23 8 The EliminationAddition Mechanism of Nucleophilic Aromatic

Aryl Halides Undergo Substitution When Treated With Very Strong Bases Cl KNH 2, NH

Regiochemistry new substituent becomes attached to either the carbon that bore the leaving group

Regiochemistry CH 3 NH 2 Na. NH 2, NH 3 CH 3 – 33°C

Same result using 14 C label * KNH 2, NH 3 Cl – 33°C

Benzyne H H Benzyne has a strained triple bond. It cannot be isolated in

Mechanism Step 3 NH 2 H H • • – H • • NH

Hydrolysis of Chlorobenzene labeling indicates that the hightemperature reaction of chlorobenzene with Na. OH

Other Routes to Benzyne can be prepared as a reactive intermediate by methods other

Other Routes to Benzyne Br • • F • • Mg, THF heat Mg.

Benzyne as a Dienophile Benzyne is a fairly reactive dienophile, and gives Diels-Alder adducts

Benzyne as a Dienophile Br + F Mg, THF heat (46%)

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23. 8 The Elimination-Addition Mechanism of Nucleophilic Aromatic Substitution: Benzyne

Aryl Halides Undergo Substitution When Treated With Very Strong Bases Cl KNH 2, NH 3 NH 2 – 33°C (52%)

Regiochemistry new substituent becomes attached to either the carbon that bore the leaving group or the carbon adjacent to it CH 3 Br Na. NH 2, NH 3 – 33°C CH 3 NH 2 + NH 2

Regiochemistry new substituent becomes attached to either the carbon that bore the leaving group or the carbon adjacent to it CH 3 Na. NH 2, NH 3 – 33°C Br CH 3 + NH 2

Regiochemistry CH 3 NH 2 Na. NH 2, NH 3 CH 3 – 33°C CH 3 NH 2 + + NH 2

Same result using 14 C label * KNH 2, NH 3 Cl – 33°C NH 2 * (52%) + * (48%) NH 2

Mechanism Step 1 H • • Cl • • H H H – • • NH 2 • •

Mechanism Step 1 H H • • Cl • • H H H • • – • • Cl • • • • – • • NH 2 • • H H NH 2 H compound formed in this step is called benzyne • •

Benzyne H H Benzyne has a strained triple bond. It cannot be isolated in this reaction, but is formed as a reactive intermediate.

Mechanism Step 2 H H – • • NH 2 • • H H

Mechanism Step 2 H H H – • • NH 2 • • H H – H • • NH 2 H • • H Angle strain is relieved. The two sp-hybridized ring carbons in benzyne become sp 2 hybridized in the resulting anion.

Mechanism Step 3 NH 2 H H • • – H • • NH 2 H • • H

Hydrolysis of Chlorobenzene labeling indicates that the hightemperature reaction of chlorobenzene with Na. OH goes via benzyne. * 14 C Na. OH, H 2 O Cl 395°C OH * (43%) + * (54%) OH

23. 9 Diels-Alder Reactions of Benzyne

Other Routes to Benzyne can be prepared as a reactive intermediate by methods other than treatment of chlorobenzene with strong bases. Another method involves loss of fluoride ion from the Grignard reagent of 1 -bromo-2 fluorobenzene.

Other Routes to Benzyne Br • • F • • Mg, THF heat Mg. Br • • F • • + FMg. Br

Benzyne as a Dienophile Benzyne is a fairly reactive dienophile, and gives Diels-Alder adducts when generated in the presence of conjugated dienes.

Benzyne as a Dienophile Br + F Mg, THF heat (46%)